IMR Press / FBL / Volume 26 / Issue 11 / DOI: 10.52586/5001
Open Access Original Research
Hyperglycemia results in significant pathophysiological changes of placental spiral artery remodeling and angiogenesis, further contributing to congenital defects
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1 Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
2 Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, Texas A&M University, Houston, TX 77843, USA
*Correspondence: (Linglin Xie)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2021, 26(11), 965–976;
Submitted: 4 September 2021 | Revised: 18 October 2021 | Accepted: 28 October 2021 | Published: 30 November 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Introduction: Hyperglycemic conditions achieved during pregnancy have been shown to have detrimental effects to fetal development and increase the prevalence of childhood comorbidities. However, the mechanisms in which diabetic pregnancies affect placental development and subsequently contribute to adverse health effects on the mother and offspring remain unclear. Research design and methods: Streptozotocin was used to induce gestational diabetes in mice. In this model, hyperglycemia was established at embryonic day 3.5 (E3.5). Pregnancy mass was collected at E10.5, E12.5, E14.5, and E16.5 for different assessments. Results: Both placental and embryonic weights were found to be significantly elevated at E16.5. At E14.5, a significantly larger junctional zone with increased number of glycogen trophoblasts was found in the placentas from hyperglycemic pregnancies (HG group) compared to the placentas from normoglycemic pregnancies (NG group). Importantly, the HG placenta exhibited decreased trophoblast giant cell (TGC) association and TUNEL+ cells, and increased expression of α-SMA on the spiral artery, suggesting arterial remodeling was impacted. Moreover, the interhemal membrane of the labyrinth layer, was found to be thicker in the HG placentas. Furthermore, hyperglycemia resulted in more offspring congenital defects, which were associated with a thicker interhemal membrane. Conclusions: Together, these results suggest that gestational diabetes perturbs proper placental development and function, specifically spiral artery remodeling and angiogenesis, thereby negatively impacting embryonic development.

Gestational diabetes
Spiral artery
Birth defects
Fig. 1.
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